Current Organic Synthesis - Volume 8, Issue 3, 2011

Recently, development of environmentally friendly reactions has been of central importance in modern synthetic organic chemistry. Water is among the most environmentally friendly and least expensive solvents, and therefore reactions mediated by water should constitute the ideal green chemistry. However, since many organic compounds have limited solubility in water, efficient water-mediated reactions with high selectivities and reactivities are still relatively limited, and hence there is a need for close examination of such research areas. Therefore this mini-thematic/hot topic issue focuses on review articles of recent development of various water-mediated organic reactions. The first review contributed by Vaccaro et al. focuses on the opening of epoxides in aqueous media. Expoxides are known to be among the most reactive and important building blocks in organic synthesis. Ring opening reactions of epoxide are also among the most commonly known reactions that occur in aqueous media under a variety of conditions. This review introduces various stereoselective ring opening reactions of epoxides in water, focusing on desymmetrization and kinetic resolutions, and the role of water is discussed in several examples. The second review contributed by Kobayashi et al. describes various organic reactions in water with chiral Lewis catalysts, such as aldol reactions, hydroxymethylation, Mannich-type reactions, ring opening reactions of meso-epoxides, Nazaro-type reactions, Michael reactions and alkyne addition to imines in water. For the purpose of development of efficient organic reactions in aqueous media, the concepts of Lewis Acid-Surfactant-combined catalysts and silica gel-supported Scandium catalysts with ionic liquid are also introduced. The third review contributed by Muzart et al. is an assembly of various metal-catalyzed reactions such as oxidations of allylic carbons, dihydroxylation and hydroxyalkoxylation of C=C bonds, C-C bond formation, and hydrogenation reactions in water and on water. These reactions are performed in an aqueous solution catalyzed by Cu- or Pd-complex with hydrosoluble ligands, with Pd-nanoparticles or without metal-ion catalysts. The effects of water in these reactions are also addressed. These review articles in this issue contain both published work and unpublished work disclosed only in Ph.D. theses. This guest editor hopes that these contributions will help expand the scope of water-mediated organic reactions and hence green reactions.

Water has proved to be an excellent reaction medium for the definition of highly chemically-efficient and environmentallyfriendly synthetic processes. In several cases, by exploiting the unique properties of water it has been possible to realize more selective and efficient processes than those performed in organic media, including the ring-opening of epoxides by nucleophiles. In this review article the role of water in influencing the stereoselectivity of epoxide ring-opening reactions will be presented, including the most recent examples of enzyme-catalyzed processes.

This review surveys a range of reactions in aqueous media mainly performed from the authors team, some of the results being only disclosed in PhD thesis. Hydrophilic ligands, [(HOCH2CH2NHCOCH2)2NCH2]2 or L-proline, have been used to carry out Cucatalyzed allylic benzoyloxylations and Pd-catalyzed allylic alkylations, isomerizations, telomerizations or cascade reactions. The determinant role of water has been exemplified with metal-free Tsuji-Trost type reactions. Pd nanoparticles have catalyzed in water the chemoselective hydrogenation of C=C bonds and the hydrogenolysis of epoxides. The last topic concerns efficient metal-free iodoheterocyclizations in water.

The progress of development in chiral Lewis acid catalyzed reaction in water is described. Lewis acid surfactant-combined catalyst and chiral bipyridine ligand complex realized catalytic asymmetric hydroxymethylation and ring-opening reaction in water successfully. Furthermore, silica-supported Lewis acid catalyst was applied for asymmetric hydroxylation in water.

The synthesis of highly functionalized molecules using multicomponent reactions became increasingly important in organic and medicinal chemistry. The Biginelli reaction is a typically one-pot three-component cyclocondensation between an aldehyde, a β- ketoester and urea leading to multifunctionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs), which provide various possibilities for transformation of the dihydropyrimidine core and the groups grafted on it. Over the years, the synthesis of DHPMs, also called the Biginelli compounds, has attracted considerable interest because of their interesting pharmacological and structural profiles. However, the chemistry of the Biginelli compounds was limited for a long time to their convenient synthesis via the multicomponent reaction, which was also successfully exploited for combinatorial purposes. Nevertheless, a growing number of studies published during the last decade described various transformations of adducts issued from the Biginelli multicomponent process. This paper focuses on recent developments concerning the reactivity of the Biginelli-type dihydropyrimidines. We present here an update in the chemistry of these compounds, in order to illustrate their potential for further functionalization through various reactions: N-alkylation or N-acylation, oxidation/ reduction, substitution/addition or annelation of the dihydropyrimidine ring.

In the past ten years, the development of efficient methods for the synthesis of A-ring 1,7-enyne synthons is one of the most fascinating aspects in the area of active vitamin D3 research. Many concise and practical approaches to construct A-ring 1,7-enyne fragments have been developed, leading to the synthesis of numerous biologically interesting vitamin D3 derivatives, differing in both stereochemistry and substituents in the A-ring portion of 1α,25-dihydroxyvitamin D3. In this review, synthetic methods of A-ring 1,7-enyne synthons, including modifications at the 1-, 2-, 3- and 4-positions of the vitamin D A-ring system, will be fully introduced.

The tetrapyrrolic uroporphyrinogen III is the common precursor of heme, chlorophylls, bacteriochlorophylls, vitamin B12 and related porphyrinoids. Heme is a prosthetic group of many proteins such as myoglobin and hemoglobin, and enzymes such as cytochrome P450 and peroxidase. Chlorophylls and bacteriochlorophylls are the basic components involved in electron and energy transfer in photosynthesis. Cobalamine is a prosthetic group of many enzymes such as RNA reductase and methyl transferase and is involved in various rearrangement reactions. The isolation and syntheses of heme, chlorophylls, bacteriochlorophylls, cobalamines and related porphyrinoids in milder conditions including ionic liquids have been discussed. Various reactions of metalloporphyrinoid enzymes such as oxidation, reduction, dehalogenation, carbon-carbon, carbon-hetero bond formation and polymerization have been mimicked by metalloporphyrinoids in ionic liquids under different reaction conditions. The non-covalent interactions of porphyrinoids in ionic liquids in biological processes, supramolecular chemistry, photodynamic therapy and newer materials have been reviewed. The impact of ionic liquids on agriculture and environmental science has also been surveyed.

Ionic liquids have been emerging as a versatile class of green solvents with many projected advantages compared with conventional media. They have been described as “designer solvents” whose properties such as solubility, density, refractive index, and viscosity can be adjusted to suit requirements simply by making changes to the structure of either anion or cation or both. In organic synthesis, ionic liquids have been extensively used for the variety of synthetic transformations. Recently, plethoras of nitrogen heterocycles have been synthesized using variety of structurally diverse ionic liquids. In the present review, I would account the synthesis of various kinds of nitrogen heterocycles using variety of ionic liquids from the beginning to the recent reports.